Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.

Dietary phytochemicals: As a potential natural source for treatment of Alzheimer's Disease

Alzheimer's disease(AD)is a common neurodegenerative disease,which seriously impairs human health and life.At present,scientists have proposed more than a dozen hypotheses about the pathogenesis of AD,including the tau propagation hypothesis.However,the exact ultimate pathogenic factor of AD remains unknown.Based on the current hypotheses,some anti-AD drugs(e.g.,donepezil and Ketamine)have been developed and used in clinical treatment,which fall into two main categories,acetylcholinesterase inhibitors(AChEIs)and N-methyl-D-aspartate(NMDA)receptor antagonists,the former representative drug is donepezil,and the latter representative drug is memantine.Since these drugs have undesirable side effects,it is necessary to find safer alternatives for AD treatment.Interestingly,dietary phytochemicals have the advantages of wide source,safety,and high biological activity,which is the natural route for screening anti-AD drugs.In this study,several representatives’dietary phytochemicals with anti-AD effect,including resveratrol,lycopene,gallic acid,berberine,ginsenoside Rg1,pseudoginsenoside-F11,ginsenoside Rh2,artemisinin,and torularhodin were selected from the published data over the last 10 years and their potential molecular mechanisms and clinical applications reviewed in the treatment of AD.

A novel degradable injectable HLC-HPA hydrogel with antiinflammatory activity for biomedical materials:Preparation,characterization,in vivo and in vitro evaluation

In situ injectable hydrogels,which have great potential in tissue engineering,are characterized by simple preparation,minimal invasiveness and adaptation to complex shapes.However,injectable hydrogels have higher requirements for biocompatibility and safety due to their use in vivo implantation.Therefore,in this study,a human-like collagen(HLC)-based in situ gel-forming injectable HLC-HPA hydrogel was synthesized by combining the amino group of HLC with the carboxyl group of HPA activated using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride(EDC)and N-hydroxysuccinimide(NHS),followed by crosslinking by horseradish peroxidase(HRP)and H_2O_2,and used as scaffold material for tissue engineering.The hydrogel stiffness,gel time and biodegradation rate could be easily and independently adjusted by varying the H_2O_2 and HRP concentrations.Scanning electron microscope(SEM)clarified the homogeneous porous and interconnected internal structures of the hydrogel.In vitro cell viability and in vivo degradation experiments confirmed that the HLC-HPA hydrogel had good biodegradability and excellent biocompatibility.Interestingly,in cultured macrophages,the HLC-HPA hydrogel showed anti-inflammatory activity by reducing the amount of the pro-inflammatory cytokines tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)and increasing the secretion of the anti-inflammatory cytokine interleukin-10(IL-10)induced by lipopolysaccharide(LPS).Meanwhile,in animal experiments,HLC-HPA hydrogels exhibit excellent biocompatibility and have properties of hemostasis and reduction of inflammatory response.Therefore,the HLC-HPA hydrogel prepared in this study has great potential for development for use in the biomedical field.

A biomimetic bi-layered tissue engineering scaffolds for osteochondral defects repair

Osteochondral defects are most commonly characterized by damages to both cartilage and underlying subchondral bone tissues,thus developing bi-layered scaffold that can concurrently regenerate these two specific lineages becomes challenge.In this study,the highly biomimetic bi-layered scaffolds were successfully prepared using human-like-collagen(HLC),hyaluronan(HA)and nano hydroxyapatite(HAP)particles,combined with"liquid phase synthesis"technology,freeze-drying and chemical crosslinking techniques,which was simulated the composition of natural extracellular matrix to repair osteochondral defects.This novel bilayer osteochondral graft had a seamlessly integrated layer structure,suitable pore size,high levels of porosity,and excellent mechanical properties.In vitro cell experiments of the bilayer scaffold indicated that the scaffold could promote the proliferation and adhesion of human bone marrow mesenchymal stem cells.In vivo osteochondral defects and micro-CT experiment revealed that bilayer scaffolds showed complete closure of the defect.Histology confirmed collagen and glycosaminoglycans were deposited in the new matrix of hyaline cartilage and bone in the bilayer scaffold group.Therefore,the developed bionic bilayer scaffold enhanced the regeneration of hyaline cartilage through subchondral bone formation and lateral host-tissue integration.In conclusion,this bilayer scaffold based on HLC could be used as the desired strategy for osteochondral defects regeneration.